title: Alterations in ethanol-induced accumbal transmission after acute and long-term zinc depletion.
abstract: Alcoholism is subject to extensive research, but the role of changes in metabolism caused by alcohol consumption has been poorly investigated. Zinc (Zn(2+) ) deficiency is a common metabolic aberration among alcoholics and Zn(2+) influences the function of ligand-gated ion channels, known pharmacological targets of ethanol (EtOH). Here, we investigate whether manipulation of extracellular levels of Zn(2+) modulates EtOH-induced increases of dopamine (DA) output, as measured by in vivo microdialysis in the rat, and whether voluntary EtOH consumption is altered by Zn(2+) deficiency. Our findings show that the Zn(2+) -chelating agent tricine slowly raises DA levels when perfused in the nucleus accumbens (nAc), whereas the more potent Zn(2+) chelator TPEN reduces DA levels. We also show that pre-treatment with either tricine or TPEN blocks the EtOH-induced DA elevation. Chronic Zn(2+) deficiency induced by a Zn(2+) -free diet did not affect EtOH consumption, but excitatory transmission, assessed by striatal field-potential recordings in the nAc shell, was significantly modulated both by Zn(2+) -free diet and by EtOH consumption, as compared with the EtOH naïve controls. The present study indicates that Zn(2+) influences EtOH's interaction with the brain reward system, possibly by interfering with glycine receptor and GABAA receptor function. This also implies that Zn(2+) deficiency among alcoholics may be important to correct in order to normalize important aspects of brain function.
authors.affiliation: Addiction Biology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sweden.
authors.forename: Julia
authors.initials: J
authors.lastname: Morud
authors.forename: Louise
authors.initials: L
authors.lastname: Adermark
authors.forename: Mia
authors.initials: M
authors.lastname: Ericson
authors.forename: Bo
authors.initials: B
authors.lastname: Söderpalm
mesh_terms: D000428:Alcohol Drinking / Q000378:metabolism; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D005029:Ethylenediamines / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D018009:Receptors, Glycine / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*; D015032:Zinc / Q000172:deficiency*
chemical_list: D002492:Central Nervous System Depressants; D002614:Chelating Agents; D005029:Ethylenediamines; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D000431:Ethanol; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine; D005998:Glycine; D004298:Dopamine; C100184:tricine
keywords: Electrophysiology; GABA; GlyR; ethanol consumption; microdialysis